Back to Search
Start Over
Identification of LZTFL1as a candidate effector gene at a COVID-19 risk locus
- Source :
- Nature Genetics; November 2021, Vol. 53 Issue: 11 p1606-1615, 10p
- Publication Year :
- 2021
-
Abstract
- The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) disease (COVID-19) pandemic has caused millions of deaths worldwide. Genome-wide association studies identified the 3p21.31 region as conferring a twofold increased risk of respiratory failure. Here, using a combined multiomics and machine learning approach, we identify the gain-of-function risk A allele of an SNP, rs17713054G>A, as a probable causative variant. We show with chromosome conformation capture and gene-expression analysis that the rs17713054-affected enhancer upregulates the interacting gene, leucine zipper transcription factor like 1 (LZTFL1). Selective spatial transcriptomic analysis of lung biopsies from patients with COVID-19 shows the presence of signals associated with epithelial–mesenchymal transition (EMT), a viral response pathway that is regulated by LZTFL1. We conclude that pulmonary epithelial cells undergoing EMT, rather than immune cells, are likely responsible for the 3p21.31-associated risk. Since the 3p21.31 effect is conferred by a gain-of-function, LZTFL1may represent a therapeutic target.
Details
- Language :
- English
- ISSN :
- 10614036 and 15461718
- Volume :
- 53
- Issue :
- 11
- Database :
- Supplemental Index
- Journal :
- Nature Genetics
- Publication Type :
- Periodical
- Accession number :
- ejs58202996
- Full Text :
- https://doi.org/10.1038/s41588-021-00955-3